Serum Perfluoroalkyl Substances Research Articles

Associations between perfluoroalkyl substances and serum lipids in a Swedish adult population with contaminated drinking water

BackgroundExposures to perfluoroalkyl substances (PFAS) have shown positive associations with serum lipids in previous studies. While many studies on lipids investigated associations with perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), there are only a few studies regarding other PFAS, such as perfluorohexane sulfonic acid (PFHxS). The purpose of the current study is to investigate if associations with serum lipids were present, not only for serum PFOS and PFOA, but also for PFHxS, and if the associations with PFAS remained also in a comparison based only on residency in areas with contrasting exposure to PFAS.Methods1945 adults aged 20–60 were included from Ronneby, Sweden, a municipality where one out of two waterworks had been heavily contaminated from aqueous fire-fighting foams, and from a nearby control area. The exposure was categorized based on either been living in areas with contrasting PFAS exposure or based on the actual serum PFAS measurements. Regression analyses of serum lipids were fitted against serum PFAS levels, percentile groups, smooth splines and between exposed and reference areas, adjusting for age, sex and BMI.ResultsDrinking water contamination caused high serum levels of PFOS (median 157 ng/ml) and PFHxS (median 136 ng/ml) and PFOA (median 8.6 ng/ml). These serum PFAS levels in the exposed groups were 5 to 100-fold higher than in the controls. In this population with mixed PFAS exposure, predominantly PFOS and PFHxS, PFAS exposure were positively associated with serum lipids. This was observed both when quantifying exposure as contrast between exposed and controls, and in terms of serum PFAS. Due to high correlations between each PFAS, we cannot separate them.ConclusionsIn conclusion, the present study provides further evidence of a causal association between PFAS and serum lipids, especially for PFHxS.

Incidence of ocular conditions associated with perfluoroalkyl substances exposure: Isomers of C8 Health Project in China

The detrimental effects of perfluoroalkyl substances (PFASs) on several physiological systems have been reported, but the association of PFASs with eye, one of the most sensitive and exposed organ, has never been explored. To investigate the association between eye diseases including visual impairment (VI) and PFASs isomers, a cross-sectional stratified study was conducted in 1202 Chinese population, aged 22–96 years, from Shenyang, China. A standard protocol including Snellen vision chart, slit-lamp microscopy and direct ophthalmoscopy was used to examine eye diseases/conditions relating to anterior and posterior segment of eyes. In addition, we measured the blood concentrations of 19 linear and branched PFASs at one-time point. Results indicated that blood levels of PFASs were significantly higher in eye disease group than normal group. PFASs exposure were positively associated with both combined eye diseases and individual eye diseases. Among other PFASs, linear perfluorooctane sulfonate (n-PFOS; odds ratio [OR] = 3.37, 95% confidence interval [CI]: 2.50, 4.56), branched perfluorooctane sulfonate (Br-PFOS; OR = 2.25, 95% CI: 1.72, 2.93) and linear perfluorooctanoic acid (n-PFOA; OR = 1.79, 95% CI: 1.36, 2.37) significantly increases the odds of VI. Vitreous disorder was adversely associated with long-chain PFASs exposure. For example, perfluorotridecanoic acid (PFTrDA; OR = 1.86, 95% CI: 1.51, 2.29) and perfluorodecanoic acid (PFDA; OR = 1.79, 95% CI: 1.36, 2.36) showed the most significant association. In conclusion, this study suggests higher serum PFASs levels were associated with increase odds of VI and vitreous disorder in Chinese adults.

Poly- and perfluoroalkyl substances in maternal serum: Method development and application in Pilot Study of the Japan Environment and Children's Study

Poly- and perfluoroalkyl substances (PFAS) have been investigated in a number of cohort studies due to concern over their adverse health effects. The aim of this study was to develop a reliable, high throughput and cost-effective analytical method for a broad range of PFAS in human serum. Protein precipitation, automatic solid phase extraction (SPE) pre-treatment and column-switching LC-MS/MS were employed. The optimised and validated method was then used to analyse the levels of 28 PFAS in 339 maternal serum samples from Pilot Study of the Japan Environment and Children's Study. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnA) and perfluorooctane sulphonic acid (PFOS) were detected in all 339 samples at median (range) concentrations of 1.9 (0.46–15), 1.5 (0.32–10), 1.3 (0.25–4.5) and 3.7 (0.43–15) ng/ml, respectively. These levels are comparable to those reported in previous studies using samples collected from various parts of the world. With a few exceptions, the remainder of the PFAS examined had lower detection rates but were found at concentrations similar to those reported in previous studies. The sensitivity and throughput ability of the method developed here are sufficient for its application in a large-scale biomonitoring study.

Perfluoroalkyl Substances and Metabolic Syndrome in Firefighters: A Pilot Study.

To compare association of perfluoroalkyl substances (PFASs) with metabolic syndrome (MetS) profile among firefighters (FF) at airport to suburban FF. Cross-sectional exploratory study, 47 men FF aged 18 to 62 years were enrolled from two fire departments in Ohio. Association between MetS outcome and log transformed serum concentrations of four PFASs was evaluated using multivariable logistic regression. PFASs serum concentrations were 18% to 74% higher in FF than the general population, and 21% to 62% higher in airport FF than suburban FF. Compared with US general population, an elevated risk of hypertension was noted in FF, but no significant association between PFASs and MetS was found. Current serum PFASs in FF are not associated with MetS risk.

Prenatal exposure to perfluorodecanoic acid is associated with lower circulating concentration of adrenal steroid metabolites during mini puberty in human female infants. The Odense Child Cohort

BackgroundFetal programming of the endocrine system may be affected by exposure to perfluoroalkyl substances (PFAAs), as they easily cross the placental barrier. In vitro studies suggest that PFAAs may disrupt steroidogenesis. “Mini puberty” refers to a transient surge in circulating androgens, androgen precursors, and gonadotropins in infant girls and boys within the first postnatal months. We hypothesize that prenatal PFAA exposure may decrease the concentrations of androgens in mini puberty. ObjectivesTo investigate associations between maternal serum PFAA concentrations in early pregnancy and serum concentrations of androgens, their precursors, and gonadotropins during mini puberty in infancy. MethodsIn the prospective Odense Child Cohort, maternal pregnancy serum concentrations of five PFAAs: Perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were measured at median gestational week 12 (IQR: 10, 15) in 1628 women. Among these, offspring serum concentrations of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), androstenedione, 17-hydroxyprogesterone (17-OHP), testosterone, luteinizing (LH) and follicle stimulating hormones (FSH) were measured in 373 children (44% girls; 56% boys) at a mean age of 3.9 (±0.9 SD) months. Multivariate linear regression models were performed to estimate associations. ResultsA two-fold increase in maternal PFDA concentration was associated with a reduction in DHEA concentration by −19.6% (95% CI: −32.9%, −3.8%) in girls. In girls, also, the androstenedione and DHEAS concentrations were decreased, albeit non-significantly (p < 0.11), with a two-fold increase in maternal PFDA concentration. In boys, no significant association was found between PFAAs and concentrations of androgens, their precursors, and gonadotropins during mini puberty. ConclusionPrenatal PFDA exposure was associated with significantly lower serum DHEA concentrations and possibly also with lower androstenedione and DHEAS concentrations in female infants at mini puberty. The clinical significance of these findings remains to be elucidated.

Are perfluorooctane sulfonate alternatives safer? New insights from a birth cohort study

BackgroundExperimental studies show that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA 6:2 and 8:2), one of perfluoroalkyl substances (PFAS) used as perfluorooctane sulfonate (PFOS) alternatives, are reproductive toxicants in vivo and in vitro. However, the associations between gestational exposure to Cl-PFESAs and birth outcomes are unknown. ObjectivesWe investigated associations between 6:2 Cl-PFESA and 8:2 Cl-PFESA in maternal serum and birth outcomes. MethodsWe measured four PFAS, including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in third-trimester maternal serum collected from 372 mother-child dyads participating in the Guangzhou Birth Cohort Study. Characteristics of mothers and infants were gathered from medical records and by interviewer-administered questionnaires. ResultsPFOS was the most abundant PFAS in maternal serum (median: 7.15 ng/mL), followed by 6:2 Cl-PFESA (median: 2.41 ng/mL). Greater maternal serum levels of all PFAS alternatives were significantly associated with lower birth weight, adjusted for confounding variables. For example, each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was associated with a 54.44 g [95% confidence interval (CI): −95.66, −13.22] and 21.15 g (95% CI: −41.44, −0.86) lower birth weight, respectively. Greater continuous maternal serum 6:2 Cl-PFESA (OR: 2.67, 95% CI: 1.73, 4.15) and PFOS (OR: 2.03, 95% CI: 1.24, 3.32) were also associated with higher risks for preterm birth, adjusted for confounders, with a possible threshold effect at the highest quartile of 6:2 Cl-PFESA. ConclusionsFor the first time, we report associations between maternal serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and adverse birth outcomes. Our findings suggest that PFOS alternatives may be reproductive toxicants in human populations and should be considered with caution before widespread use. Given the preliminary nature of our results, additional epidemiological and toxicological investigations are needed to more definitively assess the risks.

High trans-placental transfer of perfluoroalkyl substances alternatives in the matched maternal-cord blood serum: Evidence from a birth cohort study

BackgroundRecent studies suggest that perfluoroalkyl substances (PFAS) and PFAS alternatives can cross the placental barrier. However, little is known on the differential patterns of trans-placental transfer (TPT) among conventional PFAS and PFAS alternatives in epidemiological study. ObjectivesWe aimed to characterize comprehensive TPT patterns in conventional PFAS and PFAS alternatives using matched maternal-cord blood serum from a birth cohort. MethodsA total of 424 mother-fetus pairs were recruited from the Maoming Birth Cohort during 2015–2018. We detected 20 PFAS in cord and maternal serum using an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). TPT of PFAS was calculated via cord to maternal serum concentration ratios. ResultsBoth of PFOS alternatives (chlorinated polyfluorinated ether sulfonates, Cl-PFESAs) and PFOA short-chain alternative (perfluorobutanoic acid, PFBA) were widely detected in the cord and maternal serum. In cord serum, the predominant PFAS was PFOS (1.93 ng/mL), followed by PFBA (1.45 ng/mL), PFOA (0.75 ng/mL) and 6:2 Cl-PFESA (0.32 ng/mL). We found that the PFAS alternatives had higher TPT than PFOS and PFOA, such as PFBA vs. PFOA (median: 1.41 vs. 0.73, P < 0.001) and 8:2 Cl-PFESA vs. PFOS (median: 0.98 vs. 0.42, P < 0.001). Moreover, the TPT of 8:2 Cl-PFESA was higher than the precursor, linear and isomeric PFOS, respectively (P < 0.01). Furthermore, we found a U-shaped pattern for TPT in perfluorocarboxylic acid compounds (PFCAs) across different length of carbon chain. ConclusionOur findings suggest that PFAS alternatives may be more easily across the placenta than conventional PFAS. Given the widespread usage of PFAS alternatives, our results indicate that more research is needed to assess the potential health risks of prenatal exposure to PFAS alternatives in children.

Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort

BackgroundAsthma is the most common non-communicable disease in children. Prenatal exposure to perfluoroalkyl substances (PFASs), a group of persistent environmental chemicals with endocrine disrupting abilities, has been associated with immunomodulation and may contribute to the aetiology of asthma. We investigated the associations between prenatal exposure to five PFASs and asthma in 5-year-old children.MethodsWe studied 981 mother-child pairs within the Odense Child Cohort (OCC), Denmark. We measured perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) in maternal serum donated in early pregnancy. A standardized questionnaire based on the International Study of Asthma and Allergies in Childhood (ISAAC) was used to assess wheeze, self-reported asthma and doctor-diagnosed asthma among children at age 5 years. Associations were examined using logistic regression analyses adjusting for parity, maternal educational level, maternal pre-pregnancy BMI, asthma predisposition and child sex.ResultsAmong the 5-year-old children 18.6% reported wheeze and 7.1% reported asthma. We found no association between prenatal exposure to PFAS and doctor-diagnosed asthma or wheeze. Prenatal PFAS exposure was associated with self-reported asthma, although only significant for PFNA (OR = 1.84, 95% CI 1.03,3.23).ConclusionOur findings support the suggested immunomodulatory effects of PFASs, however, additional studies are warranted. In order to verify our findings, it is important to re-examine the children with postnatal measurements of serum PFAS concentrations and additional clinical diagnostic testing at an older age where an asthma diagnosis is more valid.

Inflammatory bowel disease and biomarkers of gut inflammation and permeability in a community with high exposure to perfluoroalkyl substances through drinking water

Perfluoroalkyl substances (PFAS) can act as surfactants and have been suggested to be capable of affecting gut mucosa integrity, a possible factor in the pathogenesis of inflammatory bowel disease (IBD). So far, only PFOA has been shown to have a positive association with ulcerative colitis. The present study aimed to investigate the association of PFAS and clinically diagnosed IBD in the Ronneby cohort, a population with high PFAS exposure (especially high PFOS and PFHxS) from Aqueous Film-Forming Foam through drinking water, using registry data. Additionally, to explore associations of PFAS with fecal zonulin and calprotectin, subclinical biomarkers of gut inflammation and permeability, in a sub-set of participants from Ronneby and Karlshamn (a nearby control municipality). The registry study included all people that ever resided in Ronneby municipality at least one year between 1980 and 2013. Yearly exposure to contaminated drinking water was assessed based on residential addresses and waterworks supply data, and the population classified by early, mid and late periods in ascending level of contamination. Diagnosed IBD cases were retrieved from the Swedish National Patient register and cause-of-death register. The Cox proportional hazards model was used to derive the hazard ratios (HRs) for diagnosed IBD. The biomarker study included 189 individuals who provided fecal samples. Serum PFAS were measured using LC-MS/MS. Fecal zonulin and calprotectin were measured using ELISA. Linear regression was used to assess the associations between measured PFAS and biomarker levels. In the registry study, no raised HRs for diagnosed IBD were found for cohort subjects with mid (1995–2004) or late period (2005–2013) exposure compared to never exposure. Early period exposure only (1985–1994) showed raised HRs for Crohn's disease (HR = 1.58, p = 0.048) and other non-specified IBD (HR = 1.38, p = 0.037). In the biomarker study, Karlshamn showed higher fecal calprotectin levels (median = 99.6 mg/kg in Karlshamn vs. 66.8 mg/kg in Ronneby, p = 0.04). A trend of decreased calprotectin with increased serum PFAS indicated higher PFAS was associated with lower degree of gut inflammation (p = 0.002). No association between serum PFAS and fecal zonulin was found. In conclusion, the present study found no consistent evidence to support PFAS exposure as a risk factor for IBD.

Multiple pathways of human exposure to poly- and perfluoroalkyl substances (PFASs): From external exposure to human blood

Exposure to PFASs may result in adverse health effects. This study aimed to characterise the exposure to PFASs from diet, house dust, indoor air, and dermal contact and the relative contribution from different external exposure pathways to human serum concentrations. Daily intakes of 18 perfluoroalkyl acids (PFAAs) and 12 PFAA precursors from diet, dust ingestion, inhalation of indoor air and dermal absorption were estimated using a comprehensive dataset comprising 61 adults from the Oslo area, Norway. Concentrations of PFAAs and PFAA precursors in house dust, indoor air, hand wipes, foods and drinks were utilised to estimate the daily intakes. Perfluorooctanesulfonate (PFOS) was the predominant PFAS in serum for this study group. On a median level, perfluorooctanoate (PFOA) contributed most to the total estimated daily intake of PFAAs, with a median intake of 280 (range: 72–1810) pg·kg bw−1·day−1, covering both direct and indirect (precursors) exposure. Out of this, only 3% (range: <1–48%) of the total PFOA intake came from indirect exposure. Dietary exposure from ingestion of food and drinks was in general the predominant exposure pathway, followed by exposure from ingestion of house dust, inhalation of indoor air, and dermal absorption, but considerable variations were observed among individuals. House dust ingestion and indoor air inhalation contributed most to the total intakes for some participants, for which most of them were among the 20% participants with the highest total estimated intakes. Some statistical significant associations between concentrations of PFASs measured in serum and estimated intakes were observed. Measured serum concentrations and modelled serum concentrations based on external exposure estimates were in the same order of magnitude for PFOS, PFHxS, PFOA, and PFNA, but only PFOA concentrations were comparable, 1.9 and 2.0 ng mL−1 for observed and modelled serum concentrations, respectively. The estimated daily intakes of PFASs in this study were lower than the health-based guidance values, e.g. the tolerable weekly intakes derived by EFSA. This study underlines the importance of performing studies considering multiple exposure pathways on an individual basis.

Associations of Exposure to Perfluoroalkyl Substances With Thyroid Hormone Concentrations and Birth Size.

Adequate thyroid function during pregnancy is essential for optimal fetal growth. Gestational exposure to perfluoroalkyl substances (PFAS) can negatively affect birth size and disrupt maternal and neonatal thyroid function, although the interrelationship is unclear. We aimed to quantify the associations between maternal serum-PFAS concentrations and birth weight, birth length, and cranial circumference. We also aimed to estimate associations between PFAS and thyroid hormone (TH) concentrations, thereby elucidating whether THs potentially mediate the associations between PFAS concentrations and birth size. We studied a population-based prospective cohort of 172 mother-singleton pairs from the Faroe Islands. Twelve PFAS were measured in maternal serum obtained at 34 weeks of gestation. THs were measured in maternal and cord serum. Associations between PFAS concentrations and birth size and TH concentrations were estimated using multivariable linear regressions. Sex-stratified analyses along with a mediation analysis were performed to estimate potential mediating effects of THs in the association between PFAS and birth outcomes. Several PFASs were negatively associated with birth weight, length, and head circumference, and a general positive association between maternal serum-PFASs and cord serum-thyroid-stimulating hormone (TSH; also known as thyrotropin) was found. For instance, a doubling in perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) was associated with a 53% (95% CI, 18%-99%) and 40% (95% CI, 8%-81%) increases in TSH concentrations, respectively. There was little evidence of sexually dimorphic associations. Overall, THs were not found to mediate associations between PFASs and birth size. In this study, several PFASs were negatively associated with birth size and increased THs; however, this did not explain lower birth weight among children exposed to PFAS.

Perfluoroalkyl substances (PFAS) exposure associated with immune markers: T &amp; B lymphocytes and natural killer (NK) cells

TPS 632: Health effects of flame retardants and plasticizers, Johan Friso Foyer, Floor 1, August 27, 2019, 3:00 PM - 4:30 PM Background. Perfluoroalkyl substances (PFAS) may be immunotoxic, but evidence on their possible association with counts of peripheral white blood cells (WBCs) and lymphocyte subsets is very scarce. This unique study addresses the association between 4 specific PFAS (PFHxS, PFOA, PFOS, and PFNA) and several immune function indicators. Methods. Both serum PFAS and White Blood Cells (WBCs) were measured in 42,782 (2005-2006) and 526 (2010) adults in the C8 Study, from an area with PFOA drinking water contamination in the Mid-Ohio Valley (USA). Additionally, the major lymphocyte subsets were measured in 2010. Cell counts were regressed on PFAS, with adjustment for potential confounders. Results. We found consistent positive and generally monotonic associations between numbers of total lymphocytes and PFHxS, PFOA, and PFOS in both surveys (range: 1.1% to 7.3% per PFAS IQR). Regarding lymphocyte subtypes, PFHxS was positively and strongly associated with T, B, and natural killer (NK) cells (range: 6.2%, 8.6%). PFOA and PFOS were both positively associated with number of CD3+ T and CD3+CD4+ T-helper cells (range: 3.0% to 6.9%), and PFOA with number of CD3+CD4+CD8+ T (‘double positive’) cells (10.5%). For PFOA but not the other PFAS, there were large differences in mean PFOA between water districts, but no exposure response between districts was evident. Other cells, particularly neutrophil percentage, showed slightly decreased trends associated with all PFAS (range: -2.8% to -0.6%).

Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study.

Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate < 20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.

Early Life Exposures to Perfluoroalkyl Substances in Relation to Adipokine Hormone Levels at Birth and During Childhood.

Birth cohort studies have linked exposure to perfluoroalkyl substances (PFASs) with child anthropometry. Metabolic hormone dysregulation needs to be considered as a potential adverse outcome pathway. We examined the associations between PFAS exposures and concentrations of adipokine hormones from birth to adolescence. We studied 80 mother-child pairs from a Faroese cohort born in 1997 to 2000. Five PFASs were measured in maternal pregnancy serum and in child serum at ages 5, 7, and 13 years. Leptin, adiponectin, and resistin were analyzed in cord serum and child serum at the same ages. We fitted multivariable-adjusted generalized estimating equations to assess the associations of PFASs at each age with repeated adipokine concentrations at concurrent and subsequent ages. We observed tendencies of inverse associations between PFASs and adipokine hormones specific to particular ages and sex. Significant associations with all adipokines were observed for maternal and child 5-year serum PFAS concentrations, whereas associations for PFASs measured at ages 7 to 13 years were mostly null. The inverse associations with leptin and adiponectin were seen mainly in females, whereas the inverse PFAS associations with resistin levels were seen mainly in males. Estimates for significant associations (P value <0.05) suggested mean decreases in hormone levels (range) by 38% to 89% for leptin, 16% to 70% for adiponectin, and 33% to 62% for resistin for each twofold increase in serum PFAS concentration. These findings suggest adipokine hormone dysregulation in early life as a potential pathway underlying PFAS-related health outcomes and underscore the need to further account for susceptibility windows and sex-dimorphic effects in future investigations.

Perfluoroalkyl acids serum concentrations and their relationship to biomarkers of renal failure: Serum and urine albumin, creatinine, and albumin creatinine ratios across the spectrum of glomerular function among US adults

Associations between selected perfluoroalkyl acids (PFAAs) and biomarkers of renal function were evaluated for US adult aged ≥ 20 years (N = 8220) in the National Health and Nutrition Examination Survey for 2005–2014. Glomerular filtration (GF) stage-stratified regression models were classified by estimated glomerular filtration rate (eGFR) with GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (eGFR 60–89 mL/min/1.73 m2), GF-3A (45–59 mL/min/1.73 m2), and GF-3B/4 (15–44 mL/min/1.73 m2). For GF-1, PFOA, PFOS, and PFHxS were positively and significantly associated with serum creatinine. Serum albumin levels were positively associated with the PFAA considered at all stages and most associations were significant. Further, PFAS serum concentration associations to serum albumin were about 2–3 times stronger at GF-3B/4 than at GF-1. In contrast, urine albumin was negatively and significantly associated with PFOA and PFHxS serum concentrations at all stages of renal function, while, PFOS and PFNA were negatively and significantly associated to urine albumin at GF-3A and GF-3B/4. Urine albumin/creatinine ratios were negatively and significantly associated with PFOA, PFOS, and, and PFHxS serum concentrations at all stages of renal function, as well as with PFNA and PFDA at GF-3A and GF-3B/4. Recent work revealed that serum PFAAs have an inverted U-shaped association to the calculated stages of renal failure based on eGFR; this work adds that albuminuria makes additional negative contributions to already existing negative associations of PFAA to eGFR in advancing stages of renal failure. We hypothesize that both progressive renal failure per se and especially renal failure with albuminuria cause the kidneys to reabsorb less and to excrete more of the PFAAs studied. We suspect this finding may generalize to some other perfluoroalkyl substances (PFAS). The findings also imply study design considerations for evaluating associations to diseases and biomarkers associated with renal failure, such as diabetes.

Serum perfluoroalkyl substances and lung function in adolescents exposed to the World Trade Center disaster

The effects of childhood exposure to perfluoroalkyl substances (PFASs) on lung function remain mostly unknown. Previous research indicates that children living or going to school near the World Trade Center (WTC) disaster were exposed to high levels of PFASs, among other toxic chemicals. To explore the effects of PFAS exposure on lung function, we measured serum PFASs in a cohort of children from the WTC Health Registry and a matched control group. Perfluorooctanesulfonate had the highest median concentrations in both groups (WTCHR = 3.72 ng/mL, Comparison = 2.75 ng/mL), while the lowest median concentrations were seen for perfluoroundecanoic acid (WTCHR = 0.12 ng/mL, Comparison = 0.01 ng/mL). Lung function outcomes were measured by spirometry, plethysmography, and oscillometry. Asthma diagnosis and serum eosinophil count were also recorded. We examined the relationships of each PFAS with lung function parameters and eosinophil count using linear regressions. Odds ratios for asthma were obtained for each PFAS using logistic regression. The effect of total PFASs on these outcomes was also assessed. All regression models were adjusted for sex, race/ethnicity, age, body mass index (BMI) and tobacco smoke exposure. We found that serum PFASs were not statistically associated with the measured lung function parameters, asthma diagnosis, or eosinophil count in this cohort (p < 0.05). These findings highlight the need for more longitudinal studies to explore the long-term effects of childhood PFAS exposure on lung function past adolescence and early adulthood.

Prenatal and childhood exposure to poly- and perfluoroalkyl substances (PFAS) and cognitive development in children at age 8 years

BackgroundToxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS’ impact on cognitive abilities. ObjectiveTo test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations. MethodsWe included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS. ResultsPrenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores. ConclusionWe did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years.

Health Status of Elderly People Living Near E-Waste Recycling Sites: Association of E-Waste Dismantling Activities with Legacy Perfluoroalkyl Substances (PFASs)

The elderly people living near electronic waste (e-waste) dismantling sites are susceptible to elevated chemical exposure, which is acerbated by hypometabolism and diminished immune tolerance. In this study, paired serum and urine samples collected from 1025 elderly people (≥60 years old) living near e-waste dismantling sites (n = 800) and reference areas (n = 225) in South China were analyzed for markers of health status and chemical exposures. Our results indicated that among all the health indicators fasting blood glucose (FBG) and urinary clinical markers were significantly higher in e-waste areas than in the reference area. Sixteen legacy perfluoroalkyl substances (PFASs) were determined in serum samples of elderly individuals living near e-waste dismantling areas (n = 171) and a reference area (n = 50). Serum PFASs concentrations in individuals from e-waste dismantling areas were significantly higher (p < 0.05) than those from the reference area, which indicated that e-waste dismantling activities a...

Temporal trends and predictors of perfluoroalkyl substances serum levels in Swedish pregnant women in the SELMA study.

BackgroundPerfluoroalkyl substances (PFAS) are used in numerous consumer products. They are persistent, bioaccumulating, and suspected to be endocrine disrupting chemicals (EDCs). A growing body of research has reported the association between PFAS exposure and adverse health effects. Concerns have been raised with special focus in childhood development.MethodsPerfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were analyzed by LC/MS/MS in serum from 1,616 pregnant women in the Swedish SELMA study. The serum samples were collected in the first trimester (median week 10). Least square geometric means (LSGM) of PFAS were estimated for each year period for, adjusted for potential determinants including parity, fish intake in the family, and mother's age.ResultsSix PFAS (PFNA, PFDA, PFUnDA, PFHxS, PFOA, and PFOS) were detected above levels of detection (LOD) in more than 99% of the SELMA women, while PFHpA, and PFDoDA were detected above LOD in 73.4% and 46.7% respectively. Parity, maternal age, maternal smoking, and fish intake during pregnancy were found to be significantly associated (p<0.05) with serum PFAS levels in the pregnant women. Finally, serum concentration of six PFAS (PFNA, PFDA, PFHxS, PFHpA, PFOA and PFOS) were significantly decreasing (range 14–31%) during the period of 30 months from 2007–2010.ConclusionsOur analysis shows that six out of eight PFAS could be identified in serum of more than 99% of SELMA subjects with a significant slightly decreasing trend for five of these compounds. Furthermore, parity, higher fish intake and mothers age are determinants for serum levels of PFAS in pregnant women.

Associations of serum perfluoroalkyl substance and vitamin D biomarker concentrations in NHANES, 2003-2010.

Perfluoroalkyl substances (PFAS) are persistent endocrine disrupting chemicals found in industrial and commercial products. Previous research has shown that other endocrine disrupting chemicals such as phthalates and bisphenol A may alter circulating levels of vitamin D; however, no research has examined associations between PFAS and vitamin D biomarkers. We conducted a cross-sectional analysis of 7040 individuals aged 12 years and older participating in the 2003-2010 cycles of the United States National Health and Nutrition Examination Survey (NHANES). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and total 25-hydroxyvitamin D [25(OH)D] were measured in serum samples. We used multivariable linear regression to estimate covariate-adjusted differences in total 25(OH)D or prevalence odds of vitamin D deficiency per log2 change in PFAS concentrations. We also assessed potential effect measure modification by gender, age, and race/ethnicity. PFAS were detected in over 98% of the samples. In adjusted models, each 2-fold increase in PFOS was associated with 0.9 nmol/L (95% CI: 0.2, 1.5) lower total 25(OH)D concentrations, with associations significantly stronger among whites (β: -1.7; 95% CI: -2.6, -0.7) and individuals older than 60 years of age (β: -1.7; 95% CI: -2.9, -0.5). Each 2-fold increase in PFHxS was associated with 0.8 nmol/L (95% CI: 0.3, 1.3) higher total 25(OH)D, and this association was not modified by age, gender, and race/ethnicity. PFOA and PFNA were not associated with total 25(OH)D. When assessing prevalence odds of vitamin D deficiency, we observed similar patterns of association with PFAS concentrations. Our results suggest that some PFAS may be associated with altered vitamin D levels in the United States population, and associations may vary by chemical, age, and race/ethnicity. Prospective epidemiological studies are needed to confirm our findings and determine their implications for vitamin D-associated health outcomes in children and adults.